Abstract

Preexisting plasma cell disorders, monoclonal gammopathy of undetermined significance, or smoldering myeloma are present in at least one-third of multiple myeloma patients. However, the proportion of patients with a preexisting plasma cell disorder has never been determined by laboratory testing on prediagnostic sera. We cross-referenced our autologous stem cell transplantation database with the Department of Defense Serum Repository. Serum protein electrophoresis, immunofixation electrophoresis, and serum free light-chain analysis were performed on all sera collected 2 or more years before diagnosis to detect a monoclonal gammopathy (M-Ig). In 30 of 90 patients, 110 prediagnostic samples were available from 2.2 to 15.3 years before diagnosis. An M-Ig was detected initially in 27 of 30 patients (90%, 95% confidence interval, 74%-97%); by serum protein electrophoresis and/or immunofixation electrophoresis in 21 patients (77.8%), and only by serum free light-chain analysis in 6 patients (22.2%). Four patients had only one positive sample within 4 years before diagnosis, with all preceding sera negative. All 4 patients with light-chain/nonsecretory myeloma evolved from a light-chain M-Ig. A preexisting M-Ig is present in most multiple myeloma patients before diagnosis. Some patients progress rapidly through a premalignant phase. Light-chain detected M-Ig is a new entity that requires further study.

Serum results before the diagnosis of myeloma. Positive results are shown by ●, ■, ▲, ×, and +. Samples that were negative for all 3 tests (ie, no M-Ig present) are shown by ○. ● represents positive SPEP, IFE, and sFLC assay; ■, positive SPEP and immunofixation; ×, positive sFLC assay only; ▲, positive IFE only; and +, serum-free light assay and immunofixation. The color indicates the myeloma isotype: red represents IgG; green, light-chain/nonsecretory; and blue, IgD. Because the sFLC assay was not available at diagnosis, all patients are depicted with ● at the time of diagnosis for clarity.

Two patterns of changes in monoclonal immunoglobulin level during progression to myeloma. (A) The change in monoclonal immunoglobulin level before the diagnosis of myeloma in patients with a diagnostic monoclonal immunoglobulin greater than 3 g/dL. (B) The change in monoclonal immunoglobulin level before the diagnosis of myeloma in patients with a diagnostic monoclonal immunoglobulin less than 3 g/dL.

An increasingly abnormal serum-free light chain ratio may be a harbinger of symptomatic myeloma. The temporal changes in monoclonal immunoglobulin level and involved serum free light-chain ratio (iFLC) are shown for 6 patients with intact immunoglobulin myeloma (A-F) and 1 patient with light-chain myeloma (G). The M-Ig is plotted on the outside axis and the iFLC ratio on the inside axis. The iFLC ratio is expressed as λ/κ for patients with clonal λ MM. For the 1 patient with light-chain myeloma (G), the involved sFLC is plotted on the outside axis and the involved free light-chain ratio is plotted on the inside axis.